FI925069A - NERVSKYDDANDE INDOLON OCH NAERA ANSLUTANDE DERIVAT - Google Patents
NERVSKYDDANDE INDOLON OCH NAERA ANSLUTANDE DERIVAT Download PDFInfo
- Publication number
- FI925069A FI925069A FI925069A FI925069A FI925069A FI 925069 A FI925069 A FI 925069A FI 925069 A FI925069 A FI 925069A FI 925069 A FI925069 A FI 925069A FI 925069 A FI925069 A FI 925069A
- Authority
- FI
- Finland
- Prior art keywords
- pct
- nervskyddande
- naera
- anslutande
- indolon
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
PCT No. PCT/US91/01470 Sec. 371 Date Nov. 6, 1992 Sec. 102(e) Date Nov. 6, 1992 PCT Filed Mar. 4, 1991 PCT Pub. No. WO91/17156 PCT Pub. Date Nov. 14, 1991.5-(1-Hydroxy-2-piperidinopropyl)-2(1H,3H)-indolone derivatives and analogs; pharmaceutical compositions thereof; methods of treating CNS disorders therewith; and intermediates useful in the preparation of said compounds.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI982654A FI982654A (en) | 1990-05-10 | 1998-12-08 | Nervous protective indolone and closely related derivatives |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US52233290A | 1990-05-10 | 1990-05-10 | |
US52233290 | 1990-05-10 | ||
PCT/US1991/001470 WO1991017156A1 (en) | 1990-05-10 | 1991-03-04 | Neuroprotective indolone and related derivatives |
US9101470 | 1991-03-04 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI925069A true FI925069A (en) | 1992-11-09 |
FI925069A0 FI925069A0 (en) | 1992-11-09 |
FI109121B FI109121B (en) | 2002-05-31 |
Family
ID=24080448
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI925069A FI109121B (en) | 1990-05-10 | 1992-11-09 | Process for the preparation of therapeutically active analogs of 5- (1-hydroxy-2-piperidinopropyl) -2- (1H, 3H) -indolone |
Country Status (30)
Country | Link |
---|---|
US (1) | US5306723A (en) |
EP (1) | EP0554247B1 (en) |
JP (1) | JPH0699423B2 (en) |
KR (1) | KR0163355B1 (en) |
CN (1) | CN1037439C (en) |
AT (1) | ATE192149T1 (en) |
AU (1) | AU642994B2 (en) |
BR (1) | BR9106432A (en) |
CA (1) | CA2080475C (en) |
CZ (1) | CZ280560B6 (en) |
DE (1) | DE69132141T2 (en) |
DK (1) | DK0554247T3 (en) |
EG (1) | EG19647A (en) |
ES (1) | ES2146578T3 (en) |
FI (1) | FI109121B (en) |
GR (1) | GR3034005T3 (en) |
HU (1) | HU221193B1 (en) |
IE (1) | IE911569A1 (en) |
IL (1) | IL98056A (en) |
MY (1) | MY107799A (en) |
NO (1) | NO301979B1 (en) |
PH (1) | PH29902A (en) |
PL (1) | PL169267B1 (en) |
PT (1) | PT97602B (en) |
RU (1) | RU2068414C1 (en) |
SK (1) | SK280833B6 (en) |
TW (1) | TW198720B (en) |
WO (1) | WO1991017156A1 (en) |
YU (1) | YU48528B (en) |
ZA (1) | ZA913494B (en) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2108557A1 (en) * | 1991-04-18 | 1992-10-19 | Bertrand L. Chenard | Prodrug esters of phenolic 2-piperidino-1-alkanols |
US5594007A (en) * | 1991-04-18 | 1997-01-14 | Pfizer Inc. | Method for treating spinal cord trauma with phenolic 2-piperidino-1-alkanols |
PL169884B1 (en) * | 1991-07-17 | 1996-09-30 | Pfizer | Method of obtaining novel 2-(4-hydroxypiperidino)-1-alkanolic derivatives |
FR2688504B1 (en) * | 1992-03-13 | 1995-05-05 | Synthelabo | DERIVATIVES OF 2- (PIPERIDIN-1-YL) ETHANOL, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION. |
US5319096A (en) * | 1992-04-03 | 1994-06-07 | Hoechst-Roussel Pharmaceuticals Inc. | (1H-indol-1-yl)-2-(amino) acetamides and related (1H-indol-1-yl)-(aminoalkyl)amides, pharmaceutical composition and use |
US6255322B1 (en) | 1992-06-19 | 2001-07-03 | Pfizer Inc. | 2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents |
US5436255A (en) * | 1992-07-23 | 1995-07-25 | Pfizer Inc. | Method of treating diseases susceptable to treatment by blocking NMDA-receptors |
NZ255074A (en) * | 1992-10-30 | 1996-10-28 | Pfizer | 6-[2-(4-hydroxy-4-(4-substituted phenyl)piperidino)-1-hydroxypropyl]-3,4-dihydro-2(1h)-quinolones |
US5498610A (en) * | 1992-11-06 | 1996-03-12 | Pfizer Inc. | Neuroprotective indolone and related derivatives |
KR100224961B1 (en) * | 1994-08-18 | 1999-10-15 | 디. 제이. 우드 | Neuroprotective 3-(piperidinyl-1)-chroman-4,7-diol and 1-(4-hydrophenyl)-2-(piperidinyl-1)-alkanol derivatives |
GB9510459D0 (en) | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
ZA9610738B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | Subtype selective nmda receptor ligands and the use thereof |
ZA9610741B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
ZA9610736B (en) * | 1995-12-22 | 1997-06-27 | Warner Lambert Co | 2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists |
ZA9610745B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
TW427978B (en) * | 1996-02-03 | 2001-04-01 | Hoffmann La Roche | Tetrahydroisoquinoline derivatives |
CA2251851A1 (en) * | 1996-05-13 | 1997-11-20 | Roger Salmon | Bicyclic amines as insecticides |
GB9623944D0 (en) * | 1996-11-15 | 1997-01-08 | Zeneca Ltd | Bicyclic amine derivatives |
GB9624114D0 (en) * | 1996-11-20 | 1997-01-08 | Zeneca Ltd | Pesticidal bicyclic amine derivatives |
GB9624611D0 (en) * | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Bicyclic amine compounds |
TR199901704T2 (en) | 1996-11-26 | 1999-12-21 | Zeneca Limited | 8-azabicyclo $ 3.2.1] octan-, 8-azabicyclo $ 3.2.1] oct-6-en-, 9-azabicyclo $ 3.3.1] nonan-, 9-aza-3-oxabicyclo $ 3.3.1] nonan-ve 9- aza-3-tiabicyclo $ 3.3.1] breadcrumbs, which are not prepared and used as insecticides. |
EP0846683B1 (en) * | 1996-12-03 | 2001-09-19 | F. Hoffmann-La Roche Ag | 4-Hydroxy-piperidine derivatives |
CA2220649C (en) | 1996-12-03 | 2007-02-13 | F. Hoffmann-La Roche Ag | 4-hydroxy-piperidine derivatives |
EP1173254A2 (en) * | 1999-04-27 | 2002-01-23 | Smithkline Beecham Plc | Novel treatment of neurotraumatic conditions with a raf inhibitor |
US6380205B1 (en) | 1999-10-29 | 2002-04-30 | Merck & Co., Inc. | 2-cyclohexyl quinazoline NMDA/NR2B antagonists |
US6495561B2 (en) | 1999-10-29 | 2002-12-17 | Merck & Co., Inc. | 2-cyclohexyl imidazopyridine NMDA/NR2B antagonists |
US6489477B1 (en) | 1999-10-29 | 2002-12-03 | Merck & Co., Inc. | 2-aza-bicyclo[2.2.2]octane NMDA/NR2B antigonists |
US6362196B1 (en) | 1999-10-29 | 2002-03-26 | Merck & Co., Inc. | Method to treat pain utilizing benzimidazole NMDA/NR2B antagonists |
US6476041B1 (en) | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
US6291499B1 (en) | 1999-10-29 | 2001-09-18 | Merck & Co., Inc. | 2-cyclohexyl benzimidazole NMDA/NR2B antagonists |
US6369076B1 (en) | 1999-10-29 | 2002-04-09 | Merck & Co. Inc. | 5-benzyl-octahydroindole and 6-benzyl-decahydroquinoline NMDA/NR2B antagonists |
US6432976B1 (en) | 1999-10-29 | 2002-08-13 | Merck & Co., Inc. | 8-aza-bicyclo[3.2.1]octane NMDA/NR2B antagonists |
US6316474B1 (en) | 1999-10-29 | 2001-11-13 | Merck & Co., Inc. | 2-benzyl and 2-heteroaryl benzimidazole NMDA/NR2B antagonists |
IL157254A0 (en) | 2001-02-23 | 2004-02-19 | Merck & Co Inc | N-substituted nonaryl-heterocyclic nmda/mr2b antagonists |
WO2002080928A1 (en) * | 2001-04-03 | 2002-10-17 | Merck & Co., Inc. | N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists |
EP1472248A1 (en) * | 2002-01-17 | 2004-11-03 | Eli Lilly And Company | Modulators of acetylcholine receptors |
US6713490B2 (en) | 2002-04-26 | 2004-03-30 | Pfizer, Inc. | 3,4-dihydroquinolin-2(1H)-one compounds as NR2B receptor antagonists |
EP1673367A1 (en) * | 2003-10-08 | 2006-06-28 | Pfizer, Inc. | Fused lactam compounds |
EP1838705A2 (en) * | 2005-01-13 | 2007-10-03 | Neurosearch A/S | 3,8-substituted 8-aza-bicyclo [3.2.1] octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
US20220218640A1 (en) | 2021-01-14 | 2022-07-14 | Rob Dickerman | Amino acid delivery system |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
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US3294804A (en) * | 1961-01-27 | 1966-12-27 | Sterling Drug Inc | 1-(3-hydroxy-3-phenylpropyl)-4-phenyl-4-propionoxy-piperidine |
FR5733M (en) * | 1966-09-27 | 1968-01-22 | ||
JPS51118772A (en) * | 1975-04-09 | 1976-10-18 | Otsuka Pharmaceut Co Ltd | Method for preparing carbostyryl derivatives |
US4082755A (en) * | 1977-02-14 | 1978-04-04 | Janssen Pharmaceutica N.V. | 1-[(Diarylmethyl)aminoalkyl]piperidimes |
WO1980000152A1 (en) * | 1978-07-03 | 1980-02-07 | Sandoz Ag | 3-aminopropoxy-aryl derivates,preparation and use thereof |
PH17194A (en) * | 1980-03-06 | 1984-06-19 | Otsuka Pharma Co Ltd | Novel carbostyril derivatives,and pharmaceutical composition containing the same |
US4358456A (en) * | 1980-05-03 | 1982-11-09 | John Wyeth & Brother Limited | Antipsychotic piperidinomethyl-indole derivatives |
DE3045688A1 (en) * | 1980-12-04 | 1982-07-08 | C.H. Boehringer Sohn, 6507 Ingelheim | NEW 8-ARYLALKYL-3-PHENYL-3-NORTROPANOLE, THE ACID ADDITION SALTS THEREOF, THE MEDICINAL PRODUCTS CONTAINING THE SAME AND METHOD FOR THE PRODUCTION THEREOF |
JPS57142972A (en) * | 1981-02-27 | 1982-09-03 | Otsuka Pharmaceut Co Ltd | Carbostyril derivative |
FR2534580A1 (en) * | 1982-10-13 | 1984-04-20 | Synthelabo | PHENYL-1 PIPERIDINO-2 PROPANOL DERIVATIVES, THEIR PREPARATION, AND MEDICINES THAT CONTAIN THEM |
FR2546166B1 (en) * | 1983-05-19 | 1985-10-25 | Synthelabo | ENANTIOMERS OF ERYTHRO (BENZYL-4 PIPERIDINO) -2 (HYDROXY-4 OR BENZYLOXY-4 PHENYL) -1 PROPANOL, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
FR2581993B1 (en) * | 1985-05-14 | 1988-03-18 | Synthelabo | (BENZOYL-4 PIPERIDINO) -2 PHENYL-1 ALCANOLS DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
KR910006138B1 (en) * | 1986-09-30 | 1991-08-16 | 에자이 가부시끼가이샤 | Cyclic amine derivatives |
EP0322361A3 (en) * | 1987-12-23 | 1990-01-24 | Ciba-Geigy Ag | Hydrogenated 1-benzooxacycloalkyl pyridine-carboxylic-acid compounds |
FR2640266B2 (en) * | 1988-07-12 | 1992-07-10 | Synthelabo | INDOLONES-2, QUINOLEINONES-2, BENZO (B) AZEPINONES-2 AND BENZIMIDAZOLONES-2 DERIVATIVES OF (HYDROXY-1 PIPERIDINYL-2 ALKYL), THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
ES2098248T3 (en) * | 1989-05-17 | 1997-05-01 | Pfizer | DERIVATIVES OF 2-PIPERIDINE-1-ALCANOLS AS ANTI-ISCHEMICAL AGENTS. |
-
1991
- 1991-03-04 BR BR919106432A patent/BR9106432A/en not_active Application Discontinuation
- 1991-03-04 WO PCT/US1991/001470 patent/WO1991017156A1/en active IP Right Grant
- 1991-03-04 AU AU74565/91A patent/AU642994B2/en not_active Ceased
- 1991-03-04 HU HU9203515A patent/HU221193B1/en not_active IP Right Cessation
- 1991-03-04 PL PL91296711A patent/PL169267B1/en not_active IP Right Cessation
- 1991-03-04 KR KR1019920702794A patent/KR0163355B1/en not_active IP Right Cessation
- 1991-03-04 CA CA002080475A patent/CA2080475C/en not_active Expired - Fee Related
- 1991-03-04 JP JP3505475A patent/JPH0699423B2/en not_active Expired - Fee Related
- 1991-03-04 AT AT91905608T patent/ATE192149T1/en not_active IP Right Cessation
- 1991-03-04 DE DE69132141T patent/DE69132141T2/en not_active Expired - Fee Related
- 1991-03-04 DK DK91905608T patent/DK0554247T3/en active
- 1991-03-04 RU RU9192016415A patent/RU2068414C1/en not_active IP Right Cessation
- 1991-03-04 EP EP91905608A patent/EP0554247B1/en not_active Expired - Lifetime
- 1991-03-04 US US07/941,118 patent/US5306723A/en not_active Expired - Fee Related
- 1991-03-04 ES ES91905608T patent/ES2146578T3/en not_active Expired - Lifetime
- 1991-04-02 TW TW080102540A patent/TW198720B/zh active
- 1991-04-24 PH PH42344A patent/PH29902A/en unknown
- 1991-05-03 IL IL9805691A patent/IL98056A/en not_active IP Right Cessation
- 1991-05-08 SK SK1354-91A patent/SK280833B6/en unknown
- 1991-05-08 EG EG27191A patent/EG19647A/en active
- 1991-05-08 PT PT97602A patent/PT97602B/en active IP Right Grant
- 1991-05-08 ZA ZA913494A patent/ZA913494B/en unknown
- 1991-05-08 CZ CS911354A patent/CZ280560B6/en not_active IP Right Cessation
- 1991-05-08 MY MYPI91000778A patent/MY107799A/en unknown
- 1991-05-09 IE IE156991A patent/IE911569A1/en not_active IP Right Cessation
- 1991-05-09 YU YU81091A patent/YU48528B/en unknown
- 1991-05-09 CN CN91103022A patent/CN1037439C/en not_active Expired - Fee Related
-
1992
- 1992-11-09 FI FI925069A patent/FI109121B/en not_active IP Right Cessation
- 1992-11-09 NO NO924310A patent/NO301979B1/en not_active IP Right Cessation
-
2000
- 2000-07-24 GR GR20000401691T patent/GR3034005T3/en not_active IP Right Cessation
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Legal Events
Date | Code | Title | Description |
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MA | Patent expired |